The goal of this project is to develop a quantitative molecular breast imaging PET (QMBI-PET) scanner to improve the way in which breast cancer therapies are matched to individual patients by providing evaluation of therapy efficacy during the window of opportunity between diagnosis and surgical resection. More than 250,000 women in the US with invasive disease start therapy for breast cancer each year. In 2016 approximately 40,000 deaths will result from breast cancer. Unfortunately, despite the successes of targeted therapies, the relapse rate in patients expressing the targets and receiving these therapies still approaches 50% for certain phenotypes. The drugs can be very costly, and carry toxic side effects. There are currently 68 FDA approved breast cancer drugs, the most of any cancer. PET holds great promise to improve therapy selection, thereby sparing patients from ultimately ineffective drugs and directing them more quickly to effective regimens, thus improving patient outcomes, and reducing costs via a more efficient therapy selection process. However, all of the studies thus far using PET to assess therapy response have been limited to the quantitative accuracy of clinical whole-body PET scanners A compact, lower-cost, high resolution, and quantitatively accurate PET imaging scanner will help inform the physician's choices of effective therapies for breast cancer patients. Early evaluation of a therapy's effectiveness will help the treating physician individualize a patient's treatment: In the neo-adjuvant setting or the window of opportunity between diagnosis and surgery, a baseline (pre-treatment) PET image will be taken, then, after a short regimen of a targeted therapy, a second PET scan will be used to evaluate response to treatment. This will be used to guide selection and aggressiveness of post-surgery therapy. For this treatment paradigm to become broadly accepted and widely used, the minimum viable commercial scanner needs to be higher resolution, more compact, and less expensive than standard whole-body PET scanners. In addition a high level of quantitative accuracy is needed. We propose a high-resolution quantitative molecular breast imaging PET (QMBI-PET) scanner, which uses a an advanced detector architecture and statistical-based 3D imaging to acquire high-sensitivity, high-resolution images. The outcome of this Phase-I application will be a functional laboratory tested single-ring prototype scanner, with initial data on clinical feasibility to provide evidence for commercialization in the following phase of this development.